. Coordinated alteration of hepatic gene expression in fatty acid and triglyceride synthesis in LCAT-null mice is associated with altered PUFA metabolism.

We previously reported that LCAT-deficient mice develop not only low HDL-cholesterol but also hypertriglyceridemia, hepatic triglyceride (TG) overproduction, and, unexpectedly, improved hepatic insulin sensitivity and reduced hepatic TG content. Here, we examined the mechanistic links underlying this apparent paradox. The LDL receptor-deficient (Ldlr)(-/-)xLcat(-/-) mouse model and age- and sex-matched Ldlr(-/-)xLcat(+/+) littermates, both in C57Bl/6 background, were employed. Studies of hepatic insulin signal transduction showed an upregulation of hepatic Irs2 mRNA level (5.3-fold, P = 0.02), IRS-2 protein mass level (1.5-fold, P = 0.009) and pIRS-2 (1.8-fold. P = 0.02) in the Ldlr(-/-)xLcat(-/-) mice. There was a 1.2-fold increase in pAkt (P = 0.03) with a nonsignificant change in total Akt. We observed a significant shift in its downstream transcription factor FoxO-1 to the cytosolic compartment (2.3-fold increase in cytosolic/nuclear ratio, P = 0.04). We also observed a significant 3.1-fold increase in nuclear abundance of FoxA-2 mass (P = 0.017) and a 1.5-fold upregulation of its coactivator PGC-1beta (P = 0.002), the coordinated actions of which promotes hepatic TG production and beta-oxidation. Increased hepatic insulin signaling in the Ldlr(-/-)xLcat(-/-) mice was associated with an upregulation of the Tcfe3 gene (1.7-fold, P = 0.024), a selective downregulation of the Socs-1 gene by 60% (P = 0.01), and no change in PTP-1B protein mass. These data suggest that LCAT deficiency induces complex alterations in hepatic signal transduction cascades, which explain, at least in part, the observed enhanced insulin signaling in association with hepatic TG overproduction and reduced hepatic TG content.

BackgroundConstipation is a common clinical symptom but its etiology remains unknown. The aims of the study are to discuss the relation between body mass index (BMI), motilin and the slow transit constipation (STC).MethodsA total of 178 patients with STC and 123 healthy volunteers as controls were divided into three groups according to the BMI, group A (BMI <20), group B (BMI 20-25), and group C (BMI > 25). Fasting and one hour postprandial plasma motilin were measured and the results were analyzed.ResultsThere was significant difference in the constituent ratio between STC patients and healthy controls (p < 0.05). The percentage of group A, B and C in STC patients was 49.4% (88/178), 23.0% (41/178) and 27.6% (49/178), respectively; and group A had a higher percentage. Plasma motilin of fasting and one hour postprandial in STC patients of group A was significantly lower than that of group B and C (p < 0.05), but there was no difference between group B and C (p > 0.05). There was no significant difference in the results of plasma motilin of fasting and one hour postprandial among the three groups of healthy controls (p > 0.05). Plasma motilin of fasting and one hour postprandial in STC patients of group A was significantly lower than those healthy controls of group A (p < 0.05). The same results of plasma motilin of fasting and one hour postprandial could be seen in group B and C, respectively (p < 0.05).ConclusionsA higher proportion of low BMI sufferers was found in the STC patients. The reason may be related to the lower release of the plasma motilin.

Background:PI3K/AKT pathway plays major roles in regulating cardiomyocyte metabolism. The roles of PI3K/AKT pathway and FOXO3a in mediating high glucose-induced apoptosis in cardiomyocytes remain unclear.Objectives:In this experimental study, we investigated the mechanisms of the PI3K/AKT pathway and FOXO3a in mediating hyperglycemia-induced apoptosis in neonatal rat ventricular myocytes (NRVMs).Materials and Methods:NRVMs were adopted as the cell model to investigate the roles of PI3K/AKT and FOXO3a in mediating hyperglycemia-induced apoptosis in cardiomyocytes. Annexin-V-FITC staining and PI staining were used to evaluate the apoptosis in NRVMs under indicated conditions of serum starvation, high glucose exposure, and pharmacological or genetic manipulations on the expressions of PI3K/AKT and FOXO3a. Western blotting was conducted to evaluate the cytoplasmic/nuclear localization of FOXO3a in NRVMs exposed to high glucose. FOXO3a transcriptional activity was measured by luciferase reporter assay.Results:High glucose (30 mM) induced significant apoptosis in serum-starved NRVMs as compared with normal glucose (5 mM) control (12.01 ± 0.76% vs. 2.86 ± 0.55%; P < 0.001). Treatment with IGF1 attenuated hyperglycemia-induced apoptosis by 68% (3.23 ± 0.76% vs. 9.97 ± 1.29%; P < 0.001; n = 3) in comparison with the non-treated control. Treatment with PI3K inhibitor LY294002 enhanced hyperglycemia-induced apoptosis by 109% (20.83 ± 1.87% vs. 9.97 ± 1.29%; P < 0.001; n = 3) in comparison with the non-treated control. Over-expression of AKT by transduction with CA-AKT attenuated hyperglycemia-induced apoptosis by 47% (5.48 ± 0.35% vs.10.31 ± 0.94%; P < 0.001; n = 3) in comparison with the empty-vector control. Transduction with DN-AKT enhanced high glucose-induced apoptosis by 105% (21.13 ± 1.11% vs. 10.31 ± 0.94%; P < 0.001; n = 3) in comparison with the empty-vector control. Western blotting showed that high glucose induced a significant increase in FOXO3a nuclear localization. Luciferase reporter assay showed that high glucose induced a significant increase of 310% (P < 0.001; n = 3) in FOXO3a transcriptional activity against Fas ligand when NRVMs were transducted with TM-FOXO3a in comparison with the empty-vector control.Conclusions:The PI3K/AKT pathway mediated hyperglycemia-induced apoptosis of NRVMs through the translocation of FOXO3a to nuclei and the resultant enhanced transcriptional activity of FOXO3.

The measure matching with target constraint of regional energy intensive (EI) control or overall energy consumption control (dual controls) generally owns dual energy saving effects through process technology innovation and economy structure adjustment. And the dual controls are the important countermeasures to strength national priority strategy of saving energy in recent years, whose role is to reasonably match regional agents' technical energy saving (TES) and structural energy saving (SES) in order to achieve energy saving effectively in China. With the approach of LMDI, we found that: (1) Changes in China's energy consumption structure have only promoted the substitute between different types of primary energy and have not had a significant impact on total energy consumption from 2006. (2) The single target constraint of EI is not conducive to the dual efficacy of TES and SES. Energy saving coefficient indicates that dual controls are conductive to improve energy-saving efficiency. (3) And the energy saving effect of process technology innovation went down in the period of 2015-2016 compared to the period of 2014-2015.